Chemistry:Deprenyl
Deprenyl, also known by its developmental code name E-250 and as N-propargylmethamphetamine, is the racemic mixture of D-deprenyl and L-deprenyl (selegiline).[1][2][3] It was discovered in 1961 in Hungary at Chinoin Pharmaceutical Company by Zoltan Ecseri and József Knoll, was patented in 1962, and was first described in the literature in 1964 or 1965.[1][2][3]
The drug is a monoamine oxidase inhibitor and norepinephrine–dopamine releasing agent.[2] It is a prodrug of methamphetamine and amphetamine, which mediates the latter action.[4] Deprenyl was studied clinically at high doses of 50 to 100 mg/day and was described as a psychostimulant and antidepressant.[2][1][3] At lower doses, selective MAO-B inhibition would be expected, but at these higher doses, dual inhibition of MAO-A and MAO-B would occur, on the basis of L-deprenyl.[5]
Subsequent to its synthesis, the stereoisomers of deprenyl were separated.[1] The dextrorotatory isomer, D-deprenyl, was found to be more toxic, producing effects like hyperthermia and more potent psychostimulation in rodents.[1][2] The levorotatory isomer, selegiline, was much more potent as an MAO-B inhibitor, and was subsequently developed for the treatment of Parkinson's disease and depression.[2][3]
Deprenyl is reported to result in side effects including agitation, anxiety, and sleep disturbances more often than selegiline.[6]
Similarly to selegiline, deprenyl is a catecholaminergic activity enhancer (CAE).[7] Both enantiomers of deprenyl, D-deprenyl and selegiline, are active in this respect, but selegiline is slightly more potent than D-deprenyl.[7]
Both of deprenyl's enantiomers show affinity for sigma receptors.[8][9][10][11][12]
See also
- Substituted amphetamine
- 4-Fluorodeprenyl
- AGN-1135 (racemic rasagiline)
- SU-11739 (racemic N-methylated rasagiline)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "The History of l-Deprenyl" (in de). Inhibitors of Monoamine Oxidase B. Milestones in Drug Therapy. Basel: Birkhäuser Basel. 1993. pp. 237–251. doi:10.1007/978-3-0348-6348-3_12. ISBN 978-3-0348-6349-0.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "A review of the pharmacology of selegiline". Acta Neurologica Scandinavica. Supplementum 136: 44–59. 1991. doi:10.1111/j.1600-0404.1991.tb05020.x. PMID 1686954.
- ↑ 3.0 3.1 3.2 3.3 "The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015)". Molecular Psychiatry 21 (11): 1499–1503. November 2016. doi:10.1038/mp.2016.127. PMID 27480491.
- ↑ "90 years of monoamine oxidase: some progress and some confusion". Journal of Neural Transmission 125 (11): 1519–1551. November 2018. doi:10.1007/s00702-018-1881-5. PMID 29637260.
- ↑ "Clinical pharmacokinetics and pharmacodynamics of selegiline. An update". Clinical Pharmacokinetics 33 (2): 91–102. August 1997. doi:10.2165/00003088-199733020-00002. PMID 9260033.
- ↑ "Deprenyl (selegiline): the history of its development and pharmacological action". Acta Neurologica Scandinavica. Supplementum 95: 57–80. 1983. doi:10.1111/j.1600-0404.1983.tb01517.x. PMID 6428148. "Tringer at al. (1971) (76) concluded that deprenyl has a favourable effect in endogenous depression. It was claimed by these authors that the racemic form elicited agitation, anxiety and sleep disturbances more frequently than the (-) isomer.".
- ↑ 7.0 7.1 "Multiple, small dose administration of (-)deprenyl enhances catecholaminergic activity and diminishes serotoninergic activity in the brain and these effects are unrelated to MAO-B inhibition". Archives Internationales de Pharmacodynamie et de Therapie 328 (1): 1–15. 1994. PMID 7893186.
- ↑ "Multiple sigma binding sites in the brain". Sigma Receptors. Neuroscience Perspectives. Elsevier Science. 1994. pp. 113–137 (118). ISBN 978-0-12-376350-1. https://books.google.com/books?id=ndRqAAAAMAAJ.
- ↑ "Structure-activity relationships and evolution of sigma receptor ligands (1976-present)". Sigma Receptors. Neuroscience Perspectives. Elsevier Science. 1994. pp. 45–111 (84). ISBN 978-0-12-376350-1. https://books.google.com/books?id=ndRqAAAAMAAJ.
- ↑ "Clorgyline displays high affinity for sigma binding sites in C57BL/6 mouse brain". European Journal of Pharmacology 176 (1): 107–108. January 1990. doi:10.1016/0014-2999(90)90139-w. PMID 2155796.
- ↑ "Sigma binding sites in the brain; an emerging concept for multiple sites and their relevance for psychiatric disorders". Life Sciences 47 (13): 1073–1081. 1990. doi:10.1016/0024-3205(90)90165-n. PMID 2172677.
- ↑ "Binding of sigma-ligands to C57BL/6 mouse brain membranes: effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of sigma-receptor subtypes". The Journal of Pharmacology and Experimental Therapeutics 257 (1): 141–148. April 1991. doi:10.1016/S0022-3565(25)24697-3. PMID 1850463.
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